SARS-CoV-2 has a genome made up of a single-strand RNA molecule. When it is replicated by the polymerase enzyme to make new virions, copying errors can arise in the sequence. These errors, if they are selectively advantageous, can become dominant. Early in the pandemic, the D614G mutation appeared from the Wuhan strain and quickly became dominant. It endowed the virus with greater infectivity (see the News-COVID-19.info letter, 23-29th November 2020). Researchers in Boston (at the Boston Children’s Hospital, Harvard Medical School, and Harvard Institutes of Medicine) recently analysed modifications in the spike (S) structure brought about by the D614G mutation.
The researchers carried out cryo-microscopy analysis, allowing them to study the S protein’s structure in detail. It was already known to be trimeric (involving the association of three proteins) and its RBD (Receptor Binding Domain) binds with the ACE2 receptor present on cell surfaces. This interaction causes significant changes in the S protein conformation, allowing the fusion of viral and cellular membranes to enable the entry of the virus into the cell. The RBD has two states: an “up” conformation, where the domain is accessible, and a “down” conformation which renders the RBD inaccessible to the ACE2 cellular receptor (see the News-COVID-19.info letter 4-10 January 2021).